1. Patients aged 18 years old and above. Eligibility is restricted to this age group given that the battery of neurocognitive tests utilized in this protocol are not developed or validated for use in a younger population. 2. One to four newly diagnosed brain metastases, identified on the screening MRI, from an extracranial primary tumor. 3. One lesion, designated the index lesion, is planned for surgical resection and is to be between 2.5 cm and 5.0 cm on the screening MRI. Index lesions > 2.0 cm but <2.5 cm are also eligible if surgery is deemed clinically necessary and appropriate for an attempted gross total resection by the neurosurgeon. 4. Non-index lesions must measure < 4.0 cm in maximal extent on the screening MRI brain scan. The unresected lesions will be treated with SRT as outlined in the treatment section of the concept. 5. All metastases must be located > 5 mm from the optic chiasm and outside the brainstem. Dural based metastasis are eligible. 6. Previous and/or concurrent treatment with systemic therapies (e.g., chemotherapy, targeted therapeutics, immunotherapy) is permitted and must follow protocol guidelines as follows: Systemic therapy is allowed a minimum of one week from last systemic therapy cycle to surgical resection, and one week after surgical resection to allow a minimum of one week before starting/resuming systemic therapy, depending on the specific systemic agent(s), as recommended by medical/neuro-oncology. Systemic therapy is not allowed 1 day before SRT, the same day as the SRT, or 1 day after the completion of the SRT or longer, depending on the specific systemic agent(s), as recommended by medical/neuro-oncology. Agents that are delivered by implant or depot injections (such as hormonal therapies) are excluded from these restrictions. 7. KPS score of ≥70. 8. Stable systemic disease or reasonable systemic treatment options predicting a life expectancy of ≥6 months. 9. Ability to complete an MRI of the head with contrast 10. Adequate renal and hepatic function to undergo surgery, in investigators opinion. 11. For women of childbearing potential only, a negative urine or serum pregnancy test done < 7 days prior to randomization is required. Women must be willing to notify investigator immediately if they become pregnant at any time during the trial period. 12. Men and women of childbearing potential must be willing to employ adequate contraception throughout the study and for men for up to 3 months after completing treatment. 13. Subjects must be fluent in English language to allow for completion of neurocognitive tests and completion of QOL questionnaires. Non-English speaking subjects are not permitted to participate given that participation in the real time integrated neurocognitive function tests is mandatory for all patients. The psychometric properties for translated tests are either not known or not as robust. 14. Willingness and ability to provide written informed consent and HIPAA authorization prior to performance of any study-related procedures. Exclusion Criteria 1. Age <18 years. 2. KPS<70 3. Past radiation or surgical therapy to the index lesion or the newly diagnosed non-index lesion(s) is exclusionary. However, up to a total of 2 prior courses of SRT treatment to previously diagnosed lesions are allowed as long as any treated lesions are were >15mm from the index lesion. 4. Patients with >4 newly diagnosed metastases on screening MRI 5. Pregnant patients. 6. Primary germ cell tumor, small cell carcinoma, or lymphoma. 7. Leptomeningeal metastasis (LMD). Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as radiologic or clinical evidence of leptomeningeal involvement with or without positive cerebrospinal fluid (CSF) cytology. 8. Prior WBRT for brain metastases. 9. Concomitant therapy that, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study device. 10. Comorbid psychiatric or neurologic disease or injury impacting cognition, in the opinion of the treating physician, that might impair patient's ability to understand or comply with the requirements of the study or to provide consent 11. Subjects who, in the investigator's opinion, are unable to understand the protocol or to give informed consent, have a history of poor cooperation, noncompliance with medical treatment, or difficulty in returning for follow up care.

1. Age ≥ 18 years. 2. ECOG Performance Score of 2 or better/Karnofsky Performance score of 50-60 or better. 3. Biopsy-proven non-hematopoietic malignancy, except for germ cell cancer. Small cell lung carcinoma is eligible for this study. 4. Six or more metastases on diagnostic or treatment planning imaging, which include either CT Brain (with contrast) or MR Brain (with or without contrast) imaging. 5. Largest tumor <= 4 cm. 6. No prior SRS to the lesions which will be treated on protocol. 7. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). 8. Ability to understand and the willingness to sign a written informed consent. 1. Prior whole brain radiotherapy 2. Patients with leptomeningeal metastasis. (NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.) 3. Patients with life expectancy < 4 months. 4. Psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements. 5. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

• Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to enrollment on ANBL1531 (NCT03126916)
• Patient must be >= 365 days and =< 30 years of age at diagnosis
• Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; the following disease groups are eligible:
• Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:
• MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
• Age > 547 days regardless of biologic features
• Patients with INRG stage MS disease with MYCN amplification
• Patients with INRG stage L2 disease with MYCN amplification
• Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progressed to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M
• Patients >= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M
• Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:
• 1 to < 2 years: male = 0.6; female = 0.6
• 2 to < 6 years: male = 0.8; female = 0.8
• 6 to < 10 years: male = 1; female = 1
• 10 to < 13 years: male = 1.2; female = 1.2
• 13 to < 16 years: male = 1.5; female = 1.4
• >= 16 years: male = 1.7; female = 1.4
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of > 50% by echocardiogram or radionuclide angiogram
• No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
• Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
• Patients with bone marrow failure syndromes
• Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

• STEP 1 REGISTRATION: No known IDH mutation. (If tested before step 1 registration, patients known to have IDH mutation in the tumor on local or other testing are ineligible and should not be registered)
• STEP 1 REGISTRATION: Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block and hematoxylin and eosin (H&E) stained slide to be sent for central pathology review for confirmation of histology and MGMT promoter methylation status. Note that tissue for central pathology review and central MGMT assessment must be received by the NYU Center for Biospecimen Research and Development (CBRD) on or before postoperative calendar day 23. If tissue cannot be received by postoperative calendar day 23, then patients may NOT enroll on this trial as central pathology review will not be complete in time for the patient to start treatment no later than 6 weeks following surgery. Results of central pathology review and central MGMT analysis will generally be conveyed to NRG Oncology within 10 business days of receipt of tissue. Note: In the event of an additional tumor resection(s), tissue must be received within 23 days of the most recent resection and the latest resection must have been performed within 30 days after the initial resection. Surgical resection is required; stereotactic biopsy alone is not allowed because it will not provide sufficient tissue for MGMT analysis
• STEP 1 REGISTRATION: Contrast-enhanced brain MRI within 4 days after surgery
• Magnetic resonance imaging (MRI) with Axial T2 weighted FLAIR{preferred} or T2 TSE/FSE and 3D contrast-enhanced T1 sequences are required.
• 3-dimensional (3D) pre contrast-enhanced T1 sequences are strongly suggested
• STEP 1 REGISTRATION: Willing to use highly effective method of contraception for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 6 months after completing treatment; this inclusion is necessary because the treatment in this study may be significantly teratogenic
• STEP 1 REGISTRATION: The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
• STEP 2 REGISTRATION: Histopathologically proven diagnosis of glioblastoma (or gliosarcoma as a subtype of glioblastoma) confirmed by central pathology review
• STEP 2 REGISTRATION: MGMT promoter with methylation confirmed by central pathology review (See Section 10 for details). Note: Patients with tissue that is insufficient or inadequate for analysis, fails MGMT testing, or has indeterminate or unmethylated MGMT promoter are excluded. Patients with unmethylated MGMT may be considered for enrollment on NRG-BN007
• STEP 2 REGISTRATION: IDH mutation testing by at least one method (such as immunohistochemistry for IDH1 R132H) must be performed as part of standard of care and no mutation must be found (i.e IDH wildtype). (If a mutation is identified then the patient will be ineligible and must be registered as ineligible at Step 2.)
• STEP 2 REGISTRATION: History/physical examination within 28 days prior to Step 2 registration
• STEP 2 REGISTRATION: Karnofsky performance status (KPS) >= 70 within 28 days prior to Step 2 registration
• STEP 2 REGISTRATION: Neurologic function assessment within 28 days prior to Step 2 registration
• STEP 2 REGISTRATION: Age 18-70 years
• STEP 2 REGISTRATION: Hemoglobin >= 10 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 10.0 g/dl is acceptable)
• STEP 2 REGISTRATION: Leukocytes >= 2,000/mm^3
• STEP 2 REGISTRATION: Absolute neutrophil count >= 1,500/mm^3
• STEP 2 REGISTRATION: Platelets >= 100,000/mm^3
• STEP 2 REGISTRATION: Total bilirubin =< 1.5 x institutional/lab upper limit of normal (ULN)
• STEP 2 REGISTRATION: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x ULN
• STEP 2 REGISTRATION: Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
• STEP 2 REGISTRATION: Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula
• STEP 2 REGISTRATION: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
• STEP 2 REGISTRATION: For patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Note: Known positive test for hepatitis C virus ribonucleic acid (HCV ribonucleic acid [RNA]) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
• STEP 2 REGISTRATION: Known human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to step 2 registration are eligible for this trial. Testing is not required for entry into protocol
• STEP 2 REGISTRATION: Negative serum or urine pregnancy test (in persons of childbearing potential) within 7 days prior to Step 2 registration
• Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
• STEP 2 REGISTRATION: Prior therapy for tumor except for resection. For example, prior chemotherapy, immunotherapy, or targeted therapy for GBM or lower grade glioma is disallowed (including but not limited to temozolomide, lomustine, bevacizumab, any viral therapy, ipilimumab or other CTLA-4 antibody, PD-1 antibody, CD-137 agonist, CD40 antibody, PDL-1 or 2 antibody, vaccine therapy, polio or similar viral injection as treatment for the tumor, and/or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) as is prior Laser interstitial thermal therapy (LITT), Gliadel wafer, radiotherapy, radiosurgery, vaccine or other immunotherapy, brachytherapy, or convection enhanced delivery
• Note: 5-aminolevulinic acid (ALA)-mediated fluorescent guided resection (FGR) photodynamic therapy (PDT) or fluorescein administered prior to/during surgery to aid resection is not exclusionary and is not considered a chemotherapy or intracerebral agent
• STEP 2 REGISTRATION: Current or planned treatment with any other investigational agents for the study cancer
• STEP 2 REGISTRATION: Definitive clinical or radiologic evidence of metastatic disease outside the brain
• STEP 2 REGISTRATION: Prior invasive malignancy (except non-melanomatous skin cancer, cervical cancer in situ and melanoma in situ) unless disease free for a minimum of 2 years
• STEP 2 REGISTRATION: Prior radiotherapy to the head or neck that would result in overlap of radiation therapy fields
• STEP 2 REGISTRATION: Pregnancy and individuals unwilling to discontinue nursing due to the potential teratogenic effects and potential risk for adverse events in nursing infants
• STEP 2 REGISTRATION: History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or lomustine
• STEP 2 REGISTRATION: History of pulmonary fibrosis
• STEP 2 REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection requiring IV antibiotics, IV antiviral, or IV antifungal treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
• Unstable angina pectoris within 6 months prior to Step 2 registration
• Uncontrolled cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements

• >= 4 and < 18 years at time of study entry
• Patients must weigh 15 kg or greater at time of study entry
• Newly diagnosed or recurrent primary brain tumors that have not received prior cranial radiotherapy
• Planned focal, cranial or craniospinal radiation treatment for a primary brain tumor
• The patient must have receptive and expressive language skills in English, French or Spanish since the neurocognitive function and quality of life (QOL) assessment instruments are available in these languages only
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 4 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 male; 0.8 female
• Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 male; 1 female
• Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 male; 1.2 female
• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 male; 1.4 female
• Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 male; 1.4 female
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
• The patient must be able to undergo magnetic resonance imaging
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Life expectancy of less than 18 months
• Pre-existing conditions:
• Any contraindication or allergy to memantine
• Intractable seizures while on adequate anticonvulsant therapy, defined as more than one seizure per month for the past 2 months or since initiating anticonvulsant therapy
• Co-morbid systemic illnesses, psychiatric conditions, social situations, or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or would limit compliance with the study requirements
• Patients with a motor, visual, or auditory condition that precludes computerized neurocognitive assessments are not eligible to participate
• Patients with any medical condition or taking medications that lead to alterations of urine pH towards the alkaline condition (e.g., renal tubular acidosis, carbonic anhydrase inhibitors, sodium bicarbonate)
• Personal history of prior cranial or craniospinal radiotherapy is not allowed
• Note: Prior anti-cancer therapy including surgery, chemotherapy, targeted agents are allowed as per standard of care clinical treatment guidelines
• Female patients who are pregnant are excluded since fetal toxicities and teratogenic effects have been noted for the study drug. A pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who do not agree to use an effective contraceptive method for the duration of their study participation

1. Histologically confirmed GBM (MGMT unmethylated, IDH wild type) at first, second, third, or fourth recurrence after concurrent chemoradiotherapy. Patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy determined the progressive tumor to be GBM. 2. Imaging confirmation of first tumor progression or regrowth as defined by the Response Assessment in Neuro-Oncology (RANO) criteria. A minimum of 12 weeks must have elapsed from the completion of radiotherapy to study entry to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling. 3. Karnofsky Performance Status (KPS) ≥ 60%. 4. Patients must be willing and able to provide written informed consent and to comply with the study protocol as judged by the investigator. 5. Age ≥ 18 years. 6. Patients must be able to swallow oral medications. 7. For women who are of child-bearing potential and who are sexually active and who are not surgically sterile (absence of ovaries and/or uterus): to use an adequate method of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) during the treatment period and for at least 6 months after last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. For male patients who are partners of premenopausal women: agreement to use a barrier method of contraception during the treatment period and for at least 6 months after the last dose of study drug. 7.1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). 8. Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that: 8.1 Surgery must have confirmed the recurrence. 8.2 A minimum of 28 days must have elapsed from the day of surgery to study entry. For core or needle biopsy, a minimum of 7 days must have elapsed prior to study entry. 8.3 Craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomization. 9. Patients must have recovered (Common Terminology Criteria for Adverse Events CTCAE version 6] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. Minimum times from prior therapies include: 9.1 Greater than or equal to 28 days elapsed from the administration of any investigational agent. 9.2 Greater than or equal to 28 days elapsed from the administration of any prior cytotoxic agents, except ≥ 42 days from nitrosoureas. NOTE: Prior treatment with Novo-TTF therapy is allowed at initial diagnosis but must be discontinued prior to study entry. 10. GBMs of the study patients must have EGFR gene amplification, which will be detected by next generation sequencing of tumor tissue from resected sample. 11. Prior use of bevacizumab is allowed, however patient must be off of this medication for 180 days. 12. Patients must have adequate organ and marrow function as defined by the following criteria:
• ANC ≥1.5 × 10(9)/L
• Platelets ≥100 × 10(9)/L
• Hemoglobin ≥8 g/dL
• Total bilirubin ≤1.5 × ULN Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted. ALT and AST ≤3 × ULN 1. Prior treatment with an EGFR or JAK inhibitor. 2. Subjects may not be receiving any other investigational agents for the treatment of the cancer under study. 3. Patients unable to undergo brain MRI scans with IV gadolinium contrast. 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Tofacitinib 5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements. 6. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. 7. Prior history of hypertensive crisis, hypertensive encephalopathy, or inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg while on antihypertensive medication). 8. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant gastrointestinal resection that would preclude adequate absorption of the trial medications. 9. History of another malignancy in the previous 3 years, with a disease-free interval of < 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. 10. Concurrent use of Bevacizumab.

• All patients must have a pathologically confirmed diagnosis of neuroblastoma, ≤ 30.99 years of age with history of relapsed/refractory neuroblastoma.
• All patients must have completed upfront therapy with at least 4 cycles of aggressive multi-drug chemotherapy.
• Specific Criteria by Arm: Arms 1 and 2: Subjects with no active disease: i. No evidence of residual disease by CT/MRI and MIBG scan (or PET for patients who have a history of MIBG non-avid disease). o Note: Patients with residual masses detected by CT/MRI may be considered in CR if their MIBG is negative or if MIBG positive and evaluated by PET and found to have negative PET scans; biopsy confirmation may be considered if there is still reasonable concern for persistent disease but is not required. ii. No evidence of disease metastatic to bone marrow. Arm 3: Measurable or evaluable disease, including at least one of the following: Measurable tumor by CT or MRI; or a positive MIBG and PET; or positive bone marrow biopsy/aspirate in at least one site.
• Timing from prior therapy: Enrollment (first dose of DFMO) no later than 60 days from last dose of the most recent therapy.
• Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines: 1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea). 2. Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor. 3. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair. 4. Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells. 5. Anti-GD2 Monoclonal antibodies: At least 2 weeks must have elapsed since prior treatment with a monoclonal antibody. 6. XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site. 7. Stem Cell Transplant: 1. Allogeneic: No evidence of active graft vs. host disease 2. Allo/Auto: ≥ 2 months must have elapsed since transplant. 8. MIBG Therapy: At least 8 weeks since treatment with MIBG therapy
• Subjects must have a Lansky or Karnofsky Performance Scale score of 60% or higher.
• Life expectancy > 2 months
• All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to first dose of study drug unless otherwise indicated below.
• Subjects must have adequate organ functions at the time of registration:
• Hematological: Total absolute neutrophil count ANC ≥750/μL
• Liver: Subjects must have adequate liver function as defined by AST and ALT <5x upper limit of normal (Normal=45), Bilirubin <1.5x upper limit normal (Normal=1.0). Normal PT, PTT, fibrinogen.
• Renal: Adequate renal function defined as (perform one of the following): Creatinine clearance or radioisotope GFR 70 mL/min/1.73 m2 or greater or a serum creatinine based on age/gender
• Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
• Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or patients' legal representative).
• BSA of <0.25 m2.
• Subjects that received DFMO at a dose higher than 1000mg/m2 BID prior to this study are not eligible.
• Subjects that received a dose of DFMO in combination with etoposide are not eligible.
• Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
• Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from hematological and bone marrow suppression effects of prior chemotherapy.
• Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.

1. Participant is able and willing to provide informed consent (≥18 years), or informed consent is obtained by the parent or legal guardian for minor participants, with the minor providing age appropriate assent, according to local law and regulations; 2. Life expectancy ≥ 12 weeks; 3. Known high-risk neuroblastoma OR previously intermediate-risk neuroblastoma that has relapsed or progressed to high-risk, with failure to achieve complete response with standard therapy (defined as at least 4 cycles of aggressive multi-drug induction chemotherapy with or without radiation and surgery, or according to a standard high-risk treatment/neuroblastoma protocol), OR who are medically ineligible to receive standard treatment OR who are intolerant to standard treatment; 4. Adequate recovery from acute toxic effects of any prior therapy, as deemed by the Investigator or treating Sub-Investigator; 5. Adequate liver function as defined by the following laboratory values obtained within 28 days prior to administration of 64Cu-SARTATE: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN); 6. Adequate renal function; 7. Adequate laboratory parameters: Absolute neutrophil count > 1.0 x 10 9/L; Platelet count > 50 x 10 9/L; Total bilirubin <1.5 x ULN; 8. Karnofsky or Lansky performance status ≥50; 9. All participants must have a hematopoietic stem cell product available (minimum CD34+ cell dose is ≥2 x 10 6 cells/kg); 10. Sexually active participants of reproductive potential must practice an effective method of birth control while participating on this study, to avoid possible damage to the fetus. Abstinence is considered acceptable; 11. 64Cu-SARTATE uptake on the 4 hour scan (SUVmax) of any lesion equal to or higher than that of the liver in order to move on to the therapy phase of the study. 1. Participants with disease of any major organ system that would compromise their ability to tolerate therapy, as deemed by the Investigator or treating Sub-Investigator; 2. Any other active malignancy, or a history of prior malignancy within the past 3 years; 3. History of cardiac failure as evidenced by: dyspnea at rest, exercise intolerance, oxygen requirement, clinically significant cardiac dysfunction; 4. Planned administration of chemotherapy, anti-cancer cytokine therapy, immunotherapy or radiotherapy within 2 weeks prior to the administration of 64Cu-SARTATE; 5. Administration of therapeutic dose of 131I-MIBG within 8 weeks prior to the administration of 64Cu-SARTATE; 6. External beam radiation therapy (EBRT) to both kidneys or a single functioning kidney within 12 months prior to the administration of 64Cu-SARTATE; 7. Administration of any investigational agents within 21 days prior to administration of 64Cu-SARTATE; 8. Treatment with long acting somatostatin analogues (administered within 28 days prior to the administration of 64Cu-SARTATE), or short acting somatostatin analogues (administered within 24 hours prior to the administration of 64Cu-SARTATE); 9. Known sensitivity or allergy to somatostatin analogues; 10. Previous peptide receptor radionuclide therapy (PRRT); 11. Female participants who are pregnant or lactating; 12. Participants who are on hemodialysis; 13. QTc interval ≥ 0.45 seconds as measured by Screening ECG; 14. Participants with uncontrolled infection(s); 15. Any medical condition which the Investigator feels may interfere with the procedures or evaluations of the study; 16. Participants 12 months and younger will be excluded from cohorts where the planned single or cumulative administered activity is modelled to deliver a radiation dose to the marrow that exceeds 2 Gy.

• Patients with histologically proven GBM
• Newly diagnosed GBM. Prior surgery is allowed, but should not have started any other treatment such as chemotherapy, radiation treatment, and anti-angiogenic therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Women of child-bearing potential must agree to undergo a urine pregnancy screening per standard Radiology departmental protocol, in place to prevent imaging of pregnant patients. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: 1) Has not undergone a hysterectomy or bilateral oophorectomy; or 2) Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Scheduled to undergo chemoradiation.
• Subjects who have had prior chemotherapy or radiotherapy.
• Subjects may not be receiving any other investigational agents at the time of enrollment.
• Subjects must not be pregnant since pregnancy is a contraindication to administration of gadolinium-based contrast agents.
• Any contraindication to MRI per Radiology Department's routine protocol, e.g. MRI-incompatible objects, including but not limited to medical devices (e.g. pacemakers, automated implantable cardioverter defibrillators, etc.) and other foreign bodies.
• Known severe allergic reaction to Gadolinium-based contrast agents.
• Patients with sickle cell disease and patients with other hemolytic anemias (low red blood count in body).
• Patients with uncontrollable claustrophobia, severe lower back pain, and uncontrollable tremors, to the point that it would render them unable to tolerate an MRI study.

Newly Diagnosed
• Age ≥ 18 years.
• Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) established following either a surgical resection or biopsy. An MRI scan with the required imaging sequences performed within 21 days prior to randomization preferably. The post-operative MRI scan performed within 96 hours of surgery or the MRI scan performed for radiation therapy planning may serve as the MRI scan performed during screening if all required imaging sequences were obtained.
• Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization.
• Availability of tumor tissue representative of GBM from definitive surgery or biopsy. Recurrent
• Age ≥ 18 years.
• Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum radiation therapy (RT).
• Evidence of recurrent disease demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria.
• Two scans to confirm progression are required: at least 1 scan at the time of progression and 1 scan prior to the time of progression.
• Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization.
• Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed. Newly Diagnosed
• Received any prior treatment for glioma including: a. Prior prolifeprospan 20 with carmustine wafer. b. Prior intracerebral, intratumoral, or cerebral spinal fluid (CSF) agent. c. Prior radiation treatment for GBM or lower-grade glioma. d. Prior chemotherapy or immunotherapy for GBM or lower-grade glioma. Receiving additional, concurrent, active therapy for GBM outside of the trial.
• Extensive leptomeningeal disease.
• QTc > 450 msec if male and QTc > 470 msec if female.
• History of another malignancy in the previous 2 years, with a disease-free interval of < 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Recurrent
• Early disease progression prior to 3 months (12 weeks) from the completion of RT.
• More than 2 prior lines for chemotherapy administration. (NOTE: In the 1st line adjuvant setting, combination of temozolomide (TMZ) with an experimental agent, is considered one line of chemotherapy.)
• Received any prior treatment with lomustine, agents part of any of the experimental arms, and bevacizumab or other vascular endothelial growth factor (VEGF) or VEGF receptor-mediated targeted agent.
• Any prior treatment with prolifeprospan 20 with carmustine wafer.
• Any prior treatment with an intracerebral agent.
• Receiving additional, concurrent, active therapy for GBM outside of the trial
• Extensive leptomeningeal disease.
• QTc > 450 msec if male and QTc > 470 msec if female.
• History of another malignancy in the previous 2 years, with a disease-free interval of < 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.

• All patients must have a pathologically confirmed diagnosis of neuroblastoma, < 30.99 years of age and classified as high risk at the time of diagnosis. Exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible.
• All patients must be in complete remission (CR): 1. No evidence of residual disease on scan 2. No evidence of disease metastatic to bone marrow.
• Specific Criteria by Stratum: Stratum 1/1B: All patients must have completed standard upfront therapy that replicates treatment which patients who were enrolled on ANBL0032 received, including: intensive induction chemotherapy and (if feasible) resection of primary tumor, followed by: consolidation with high-dose chemotherapy with stem cell transplant and radiotherapy, followed by: immunotherapy with Ch14.18/IL-2/GM-CSF (dinutuximab) and retinoic acid;. All subjects on Stratum 1/B must have also met the following criteria: • A pre-transplant disease status evaluation that met International Neuroblastoma Response Criteria (INRC) for CR (complete response), VGPR (very good partial response), or PR (partial response) for primary site, soft tissue metastases and bone metastases. Patients who meet those criteria must also meet the protocol-specified criteria for bone marrow response prior to transplant as outlined below: No more than 10% tumor involvement (based on total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy. Stratum 2: Neuroblastoma that is in first complete remission following standard upfront therapy different from that described for Stratum 1. Stratum 3: Neuroblastoma that failed to have a response of at least PR following induction chemotherapy and surgical resection of the primary tumor, but that has achieved CR following additional therapy. Stratum 4: Patients who have achieved a second or subsequent CR following relapse(s).
• Pre-enrollment tumor survey: Prior to enrollment on this study, a determination of mandatory disease staging must be performed:
• Tumor imaging studies including
• Bilateral bone marrow aspirates and biopsy
• This disease assessment is required for eligibility and preferably should be done within 2 weeks prior to enrollment, but must be done within a maximum of 4 weeks before enrollment.
• Timing from prior therapy: Stratum 1/1B: Enrollment no later than 60 days after completion of upfront therapy, (last dose of cis-retinoic acid) with a maximum of 6 cycles of cis-retinoic acid maintenance therapy. Stratum 2, 3 and 4: Enrollment no later than 60 days from last dose of the most recent therapy.
• Patients must have a Lansky or Karnofsky Performance Scale score of > 50% and patients must have a life expectancy of ≥ 2 months.
• All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated below.
• Patients must have adequate organ functions at the time of registration:
• Hematological: Total absolute phagocyte count ≥1000/μL
• Liver: Subjects must have adequate liver function
• Renal: Adequate renal function
• Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
• Written informed consent in accordance with institutional and FDA (food and drug administration) guidelines must be obtained from all subjects (or patients' legal representative).
• BSA (Body Surface Area) of <0.25 m2.
• Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
• Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from hematological and bone marrow suppression effects of prior chemotherapy.
• Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.

1. Subjects with a diagnosis of iobenguane avid, high-risk neuroblastoma based on Revised INRC criteria at the time of study enrollment with recurrent or progressive disease at any time prior to enrollment, regardless of overall response to frontline therapy, where frontline therapy includes a minimum of 4 cycles of induction therapy at any time prior to enrollment. 2. May have had prior 131I-MIBG therapy, provided: 1. It has been at least 6 months from the date of last 131I-MIBG ; 2. Response was other than progressive disease on first restaging after 131I-MIBG ; 3. Prior 131I-MIBG was given as monotherapy and not in combination with systemic anticancer agents; 4. Cumulative lifetime dose of 131I-MIBG at enrollment does not exceed 18 mCi/kg. 3. All soft tissue lesions identified on CT/MRI scans must be iobenguane avid lesions on an (123I)-iobenguane scan, or 1. any progressive non-iobenguane avid lesion is proven by biopsy to be a non-neuroblastoma lesion. 2. any other non-avid lesion is comprised of a fibrotic or scarred mass as shown by routine imaging and confirmed by the investigator. 4. Adequate cryopreserved autologous peripheral blood stem cells or bone marrow (at least 2 aliquots of 2.0 × 10exp6 CD34/kg at the time of study enrollment). 5. If a male, must agree to use an adequate contraception method as deemed appropriate by the Investigator (e.g., vasectomy, condoms) or partner using effective contraception and to not donate sperm during the study and for 90 days after receiving the last dose of study drug. 6. If a female of childbearing potential, have a negative serum pregnancy test result prior to each dosing and, if sexually active, be practicing an effective method of birth control [e.g., intrauterine device, double-barrier method (i.e., diaphragm, or a cervical cap) with intravaginal spermicidal foam, cream or gel], or male partner sterilization throughout the study. 7. Age at study entry ≥1 year. 8. Previous platelet transfusions are permitted, as long as the subject has a platelet count ≥50,000/μL without transfusion support for at least 1 week. 9. Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline. 10. An absolute neutrophil count ≥750/μL without growth factor for 5 days. 11. Liver function parameter results: total bilirubin ≤2 × upper limit of normal for age, and Serum alanine aminotransferase (glutamic-pyruvic transaminase) and serum aspartate aminotransferase (glutamic-oxaloacetic transaminase) ≤ 10 times the upper limit of normal (for all sites, the upper limit of normal for alanine aminotransferase is defined as 45 U/L). 12. Normal thyroid function as measured by T4 or TSH or have abnormal results that are not considered clinically important by the Investigator or may be receiving levothyroxine. 13. Cardiac Function: shortening fraction of ≥ 27% by echocardiogram or ejection fraction ≥ 50% documented by echocardiogram or radionuclide angiogram within 1 month prior to Visit 1 (Baseline). 14. Karnofsky Performance Status (for subjects >16 years of age) or the Lansky Performance Status Performance Status (for subjects 1 to 16 years of age) ≥50%. 15. Full recovery from the toxic effects of any prior therapy. 16. Coagulation Function: 1. International Normalized Ratio (INR) < 1.5 2. Partial thromboplastin time (PTT) < 1.5 times upper limit of normal. 1. Subjects within 5 half-lives after any antibody-based immunotherapy, or have not recovered from effects of any biologic therapy. 2. Subjects <12 weeks after myeloablative therapy with autologous stem cell transplant. 3. Subjects who have had an allogeneic stem cell treatment less than 4 months from Visit 1 are excluded. Those who have received allogeneic stem cell treatment more than 4 months from Visit 1 must have recovered and have no active graft versus host disease (GVHD) to be eligible. 4. Subjects must not have received radiation for a minimum of 2 weeks prior to study enrollment. Subjects whose only site(s) of disease have been radiated are eligible as long as the subject has MIBG avidity 2 weeks after completion of radiation. A minimum of 12 weeks prior to study enrollment is required following prior large field radiation therapy (ie, craniospinal, whole abdominal, total lung, > 50% marrow space) 5. History of total body irradiation. 6. Subjects do not have adequate renal function defined as GFR ≥ 70 mL/min/1.73 m2 either by creatinine clearance or radioisotope direct measurement or by calculation with the Schwartz formula 7. Subjects who are on hemodialysis. 8. Pregnancy or breastfeeding. 9. Significant active infections including active hepatitis B, or hepatitis C infection, or known infection with human immunodeficiency virus (HIV) (testing for HIV is not required prior to study entry). 10. Clinically important cardiac, pulmonary, and hepatic impairment. 11. Vorinostat treatment exclusion criteria (subjects, who meet any one of these criteria and otherwise meet eligibility criteria, are still eligible for 131I-MIBG monotherapy) 1. Since valproic acid has HDAC inhibitory activity, patients must not have received valproic acid within 30 days of study entry. 2. Since vorinostat may prolong the QT interval, patients must not be receiving other medications known to prolong the QT interval at the time of study entry . Pentamidine must not have been received within 1 week of study enrollment. 3. Patients with a history of deep venous thrombosis that was not associated with the presence of a central venous catheter. 4. Patients who are receiving Coumadin.

• Patient must be newly diagnosed or relapsed/progressed with a brain tumor that has not previously been treated with CRT
• Note: COG therapeutic study participation is not required for ACCL10P1 enrollment
• Patient enrollment must occur within 4 calendar months following completion of CRT
• Reminder: after patient enrollment, baseline testing followed by randomization must occur within 2-4 months after completion of CRT
• The patient must have an identified caregiver who is willing and able to oversee the training practice during the intervention period (ie, for 5-9 weeks starting approximately 3 months after completion of CRT)
• The patient must have access to a telephone and phone number where they can be reached
• The patient and caregiver must have reading, speaking and listening comprehension of English
• All patients and/or their parents or legal guardians must sign a written informed consent (patient assent is also recommended when applicable according to each institution's policy)
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Patients with pontine glioma are not eligible
• Patients with an estimated survival of less than one year are not eligible
• Patients with a history of traumatic brain injury prior to tumor diagnosis are not eligible
• Patients with a motor, visual, or auditory handicap that prevents computer use (e.g., unresolved posterior fossa syndrome) are not eligible to participate in this trial
• Patients with full-scale intelligence quotient (IQ) < 70 per previous testing OR existing diagnosis of/educational classification as a student with an intellectual disability are not eligible

Pre-Registration
• United States (US) and Canadian sites: * This review is mandatory prior to registration to confirm eligibility; patients must be willing to submit tissue samples for mandatory central pathology review submission; it should be initiated as soon after surgery as possible
• Tissue must have been determined to have local 1p/9q co-deletion and IDH mutation prior to submission for central path review
• Tumor tissue must show co-deletion of chromosomes 1p and 19q; for eligibility, the 1p/19q analysis results will be accepted from the local site, as determined by either a locally available or reference laboratory (for US, must be Clinical Laboratory Improvement Act [CLIA] certified); acceptable methods for determination of 1p/19q loss include fluorescent in-situ hybridization (FISH), by genomic sequencing or methylomic analyses; US and Canadian sites must send a copy of the official report to the pathology coordinator and quality assurance specialist (QAS)
• Tumor must also show evidence of IDH mutation by immunohistochemistry or genomic analyses; this should be performed at the local site (US: performed in a CLIA certified laboratory); the site must send a copy of the official report to the pathology coordinator and QAS Registration
• Newly diagnosed and =< 3 months from surgical diagnosis; patients are also eligible if they have had a prior surgical procedure > 3 months earlier for low grade glioma, as long as the patient has not received prior radiation or prior chemotherapy
• Histological evidence of World Health Organization (WHO) grade III anaplastic glioma or WHO grade II low grade glioma with locally diagnosed combined 1p/19q loss and the presence of an either IDH1 or IDH2, both as established by a local or referenced laboratory qualified for the study * Note: mixed gliomas are eligible, regardless of the degree of astrocytic or oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q
• Patients with codeleted low grade gliomas must also be considered "high risk" by exhibiting one or more of the following characteristics:
• Age >= 40 and any surgical therapy
• Age < 40 with prior and subtotal resection or biopsy (i.e., anything less than gross total resection)
• Documented growth following prior surgery (NOTE: patients with prior surgery cannot have received prior radiation, chemotherapy or targeted therapy)
• Intractable seizures
• Surgery (partial or gross total resection or biopsy) must be performed >= 2 weeks prior to registration; patient must have recovered adequately from the effects of surgery
• Absolute neutrophil count (ANC) >= 1,500/mm^3 obtained =< 21 days prior to registration
• Platelet (PLTs) count >= 100,000/mm^3 obtained =< 21 days prior to registration
• Hemoglobin (Hgb) > 9.0 g/dL obtained =< 21 days prior to registration
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) obtained =< 21 days prior to registration
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN obtained =< 21 days prior to registration
• Creatinine =< 1.5 x ULN obtained =< 21 days prior to registration
• Negative serum or urine pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
• Willingness and ability to personally complete neurocognitive testing (without assistance) and willingness to complete the QOL testing, (either personally or with assistance)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
• Written informed consent
• Willingness to return to enrolling institution for follow-up during the active monitoring phase (that is, the active treatment and observation portion) of the study); patients who have been formally transferred to another active and approved site participating in this study would not need to return to the enrolling institution for this purpose
• Willingness to allow the provision of tissue samples for correlative research, as long as adequate tissues are available; patients will not be excluded from participation in the study, if they are willing to allow provision of tissues for the correlative research, but there are insufficient quantities of tissue for the correlative analyses (e.g., a patient otherwise eligible and willing who had biopsy only) Willingness to allow the provision of blood samples for correlative research; patients are not excluded from participation in the study, if they are willing to provide the mandatory biospecimens for translational/correlative research, but for logistical reasons the specimens(s) were not obtainable or if the volume collected was insufficient Registration
• The following categories are ineligible:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception or contraceptive method during this study and 6 months following the completion of chemotherapy treatments
• History of prior radiation therapy or chemotherapy for glioma; note: patients who have a history of prior low grade glioma (with or without a distant history of prior surgery for that glioma), but who have never received prior chemotherapy or radiation therapy for the glioma are eligible for the study
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Concomitant serious immunocompromised status (other than that related to concomitant steroids) that would compromise the safety of the patient on the study
• Patients known to be human immunodeficiency virus (HIV) positive and currently receiving retroviral therapy are not eligible; note: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving any other investigational agent that would be considered as a treatment for the primary neoplasm
• Other active malignancy within 5 years of registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior malignancy, the patient is not eligible if they are receiving other specific treatment (with the exclusion of hormonal therapy or Her-2 inhibitors) for their cancer or if they have received prior total body irradiation which included the brain
• History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Recent history of hepatitis infection or if the treating physician determined that the patient would be at significant risk of reactivation of hepatitis

1. At least 18 years of age 2. Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee 3. Histologically confirmed glioma 4. Progression by Response Assessment in Neuro-Oncology (RANO) criteria following standard treatment options with known survival benefit (Temozolomide, Radiation, and Tumor Treating Fields [unless unwilling]) 5. Patients who receive treatment with antiepileptic medications must have a two week history of stable dose of antiepileptic without seizures prior to dosing 6. Patients with corticosteroid requirements to control cerebral edema must be maintained at a stable or decreasing dose for a minimum of two weeks without progression of clinical symptoms 7. A volume of enhancing tumor which falls within the treatment field volume being evaluated in the respective cohort (see 4.1 Design) 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 9. Life expectancy of at least 2 months 10. Acceptable liver function:
• Bilirubin ≤ 1.5 times upper limit of normal
• AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal (ULN); 11. Acceptable renal function:
• Serum creatinine ≤1.5xULN 12. Acceptable hematologic status (without hematologic support):
• ANC ≥1000 cells/uL
• Platelet count ≥100,000/uL
• Hemoglobin ≥9.0 g/dL 13. All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose For part 2: 14. Bevacizumab naïve glioblastoma with no more than 1 recurrence 1. The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible. 2. The subject is unable to undergo MRI scan (eg, has pacemaker). 3. The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study. 4. The subject is pregnant or breast-feeding. 5. The subject has serious intercurrent illness, as determined by the treating physician, that would compromise either patient safety or study outcomes such as:
• hypertension (two or more blood pressure readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment
• Non-healing wound, ulcer, or bone fracture
• Clinically significant cardiac arrhythmias
• Untreated hypothyroidism
• Uncontrolled systemic infection
• Symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug
• Myocardial infarction, stroke, transient ischemic attack within 6 months
• Known active malignancy (other than glioma) except non-melanoma skin cancer or carcinoma in-situ in the cervix 6. The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding 7. The subject has received any of the following prior anticancer therapy:
• Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy, or intra-operative radiotherapy (IORT) to the target site.
• Radiation therapy within 12 weeks of screening
• Systemic therapy (including investigational agents and small-molecule kinase inhibitors) or non-cytotoxic hormonal therapy (eg, tamoxifen) within 14 days or 5 half-lives, whichever is shorter, prior first dose of study drug
• Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug
• Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug
• Prior treatment with carmustine wafers
• Patients who are currently receiving any other investigational agents and/or who have received an investigational agent in the prior 28 days 8. Multifocal progression or involvement of the leptomeninges 9. Psychiatric illness/social situations that would limit compliance with the study requirements 10. Infratentorial disease

• Patients must be:
• < 12 months (< 365 days) of age at diagnosis with INRG stage L1; or
• < 18 months (< 547 days) of age at diagnosis with INRG stage L2 or stage Ms neuroblastoma/ganglioneuroblastoma
• Enrollment on ANBL00B1 or APEC14B1 is required for all newly diagnosed patients
• Patients must have newly diagnosed v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) non-amplified neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or MYCN non-amplified ganglioneuroblastoma verified by histology
• Patients must meet the specified criteria for one of the treatment groups defined below; genomic features include MYCN gene amplification, segmental chromosome aberrations (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) and deoxyribonucleic acid (DNA) index
• "Favorable" genomic features are defined by one or more whole-chromosome gains or hyperdiploid tumor (DNA index > 1) in the absence of segmental chromosome aberrations as defined above
• "Unfavorable" genomic features are defined by the presence of any segmental chromosome aberration (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) or diploid tumor (DNA index = 1); this includes copy neutral loss of heterozygosity (LOH)
• Only patients with MYCN non-amplified tumors are eligible for this study
• Group A: patients < 12 months (< 365 days) of age with newly diagnosed INRG stage L1 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
• Greatest tumor diameter < 5 cm of adrenal or non-adrenal origin
• Patients with non-adrenal primaries are eligible, but must have positive uptake on metaiodobenzylguanidine (MIBG) scan or elevated catecholamine metabolites (urine or serum) to support the diagnosis of neuroblastoma
• No prior tumor resection or biopsy
• Group A will be further split into two subsets, which are mutually exclusive, for statistical purposes
• Group A1:
• > 6 months and < 12 months of age with an adrenal primary tumor < 5 cm in greatest diameter OR
• Patients less than 6 months of age with an adrenal primary tumor > 3.1 and < 5 cm in greatest diameter OR
• < 12 months of age with a non-adrenal primary site < 5 cm in greatest diameter
• Group A2: =< 6 months of age with an adrenal primary site and tumor =< 3.1 cm in greatest diameter.
• Group B: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage L2 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
• No life threatening symptoms or no impending neurologic or other organ function compromise (e.g. epidural or intraspinal tumors with existing or impending neurologic impairment, periorbital or calvarial-based lesions with existing or impending cranial nerve impairment, anatomic or mechanical compromise of critical organ function by tumor [abdominal compartment syndrome, urinary obstruction, etc.]); horner syndrome is not considered neurologic compromise
• No prior tumor resection, tumor biopsy ONLY
• Only patients with both favorable histology and favorable genomic features will remain on study as part of Group B; the institution will be notified of histologic and genomic results within 3 weeks of specimen submission on ANBL00B1 or APEC14B1
• Group C: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage Ms neuroblastoma/ganglioneuroblastoma
• No prior radiotherapy or chemotherapy, with the exception of dexamethasone, which is allowed
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Patients with MYCN amplified tumors are not eligible
• Group B and C patients who do not enroll on ANBL1232 within 4 weeks of definitive diagnostic procedure
• Group A and C patients, not required to undergo tumor biopsy, who do not enroll on ANBL1232 within 4 weeks of confirmatory imaging study

Inclusion Criteria 1. Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor. 2. Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible) 3. All brain metastases must be outside the brain stem (midbrain, pons and medulla). 4. Patient must have 10 or less brain metastases. 5. The maximum diameter of any lesion must be less than or equal to 3.0 cm. 6. Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS 7. Age ≥ 18 years. 8. ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better. 9. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Medically acceptable birth control (contraceptives) includes:
• Approved hormonal contraceptives (such as birth control pills, patch, or ring: Depo-Provera, Implanon), or
• Barrier methods (such as a condom or diaphragm) used with a spermicide (a substance that kills sperm) 10. Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria 1. Patients had craniotomy and surgery to the brain within 7 days from the date of SRS. 2. Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion. 3. Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast) 4. Patients with life expectancy < 3 months. 5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements. 6. Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

PRE-REGISTRATION ELIGIBILITY CRITERIA (ALL PATIENTS) • Tissue available for biomarker testing (any brain metastasis tissue and extracranial site from any prior resection or biopsy). REGISTRATION ELIGIBILITY CRITERIA (ALL PATIENTS)
• Participants must have histologically confirmed parenchymal metastatic disease to the brain from any solid tumor. Note: this includes patients that have controlled extracranial disease with progressive intracranial metastasis, as well as patients that have progressive intracranial and extracranial disease.
• New or progressive brain metastases are defined as any one of the following:
• Untreated measurable lesions in patients who have received surgery and/or stereotactic radiosurgery (SRS) to one or more other lesions.
• Progressive measurable lesions after radiation, surgery, or prior systemic therapy
• Residual or progressive lesions after surgery if asymptomatic.
• Patients who have had prior whole-brain radiotherapy (WBRT) and/or SRS and then whose lesions have progressed by BM-RANO criteria or there are new lesions, are eligible. Lesions treated with SRS may be eligible if there is unequivocal evidence of progression. For patients with NTRK or ROS1 mutations, entrectinib may be used for newly diagnosed brain metastases.
• Patients who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible, but such patients must be asymptomatic or neurologically stable from their CNS metastases.
• Measurable CNS disease (=> 10 mm).
• Ability to obtain magnetic resonance imaging (MRI)s with contrast
• No surgery within 2 weeks prior to or after registration.
• No chemotherapy within 14 days prior to registration (Note: for abemaciclib arm, a 21-day chemotherapy washout is required).
• For melanoma, patients must have progressed after prior immune checkpoint blockade or for BRAF positive melanoma, BRAF/MEK inhibitors.
• For lung cancer, EGFR mutant patients must have failed EGFR therapies
• For HER2-positive breast cancer patients (regardless of ER/PR status), patients must have received at least one prior HER-2 directed therapy in the metastatic setting.
• For triple negative breast cancer (TNBC), patients must have received at least one chemotherapy in the metastatic setting.
• For estrogen receptor (ER) and/or progesterone receptor (PR)+ HER2-negative breast cancer, patients must have received at least one endocrine therapy in the metastatic setting.
• Patients who have received prior treatment with any of the targeted treatments on this study are not eligible for that specific treatment arm(s), but could be eligible for other arms (e.g., a patient who has had prior treatment with abemaciclib would not be eligible for the abemaciclib arm, but could be eligible for another arm).
• Presence of clinically actionable alteration in NTRK, ROS1, or CDK pathway or PI3K pathway in both a brain metastasis and extracranial site per central review.
• Not pregnant and not nursing, because this study involves investigational agents whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required (Note: for abemaciclib arm, pregnancy test is required =< 7 days prior to registration).
• No known current diffuse leptomeningeal involvement (diffuse defined as leptomeningeal involvement throughout the CNS axis; if there is documented positive CSF cytology, patient is ineligible).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Adequate organ function.
• Absolute neutrophil count (ANC) >= 1,500/mm^3.
• Platelet count >= 100,000/mm^3.
• Total bilirubin =< 1.5 x upper limit of normal (ULN) except in patients with Gilbert's disease. Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN).
• Creatinine =< 1.5 mg/dL OR calculated (Calc.) creatinine clearance > 45 mL/min.
• No uncontrolled medical comorbidities per investigator discretion (e.g. interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)
• Radiation to symptomatic non-target sites within neural axis is allowed prior to registration without washout (provided there is at least one untreated target lesion for measurement on study and radiation is completed prior to registration).
• Concurrent systemic corticosteroids are allowed if stable dose of dexamethasone for 7 days prior to registration. Baseline doses and changes in steroid dosing will be captured.
• No concurrent administration of anticancer therapies (except for endocrine therapy or continuation of hormonal therapy or trastuzumab in breast cancer patients). No chemotherapy, targeted therapy or immunotherapy within 14 days prior to entering the study (Note: For abemaciclib arm, a 21-day chemotherapy washout is required).
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug 14 days prior to registration on the study.
• Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment. ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR PAXALISIB ARM
• Urine protein to creatinine (UPC) ratio < 1 or urine protein =< 1.
• Recent acute myocardial infarction in the last 6 months or current angina pectoris are excluded. Patients with symptomatic bradycardia should have an electrocardiogram at baseline. If QT interval > 470 msec, the patient is excluded.
• Patients with uncontrolled type I or II diabetes mellitus should be excluded. Uncontrolled diabetes is defined as glycosylated hemoglobin (HbA1c) > 9% in addition to fasting glucose > 140 mg/dL on at least 2 occasions within 14 days prior to registration. ADDITIONAL REGISTRATION ELIGIBILITY CRITERION FOR ENTRECTINIB ARM • Concurrent use of H2 receptor antagonists, receptor antagonists, proton pump inhibitors (PPIs), and/or antacids are prohibited. ADDITIONAL REGISTRATION ELIGIBILITY CRITERION FOR ABEMACICLIB ARM
• Hemoglobin >= g/dL. Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
• Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to registration. A washout period of at least 21 days is required between last chemotherapy dose and registration (provided the patient did not receive radiotherapy).
• Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and registration.
• Breast cancer patients who have received ribociclib or palbociclib are eligible as long as there is documentation of CDK4/6 pathway alteration on a biopsy or resection at the point of progression post-ribociclib or palbociclib.
• For females of childbearing potential: A female of childbearing potential, must have a negative serum pregnancy test within 7 days prior to registration and agree to use a highly effective contraception method during the treatment period and for 3 weeks following the last dose of abemaciclib. Contraceptive methods may include an intrauterine device [IUD] or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection. Cases of pregnancy that occur during maternal exposures to abemaciclib should be reported. If a patient or spouse/partner is determined to be pregnant following abemaciclib initiation, she must discontinue treatment immediately. Data on fetal outcome and breast-feeding are to be collected for regulatory reporting and drug safety evaluation.
• Patients with active bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive] are excluded. Screening is not required for enrollment.
• Patients with personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest, are excluded.

1. At least 18 years of age at time of screening. 2. Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB. 3. Subject has proven and documented LM that meets the requirements for the study: • EANO-ESMO Clinical Practice Guidelines Type 1 and 2 (with the exception of 2D) LM of any primary type. 4. Karnofsky performance status of 60 to 100 5. Acceptable liver function:
• Bilirubin ≤ 1.5 times upper limit of normal
• AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal for subjects with normal liver. * AST (SGOT) and ALT (SGPT) ≤ 5.0 times upper limit of normal for subjects with liver metastasis
• Acceptable renal function with serum creatinine ≤ 2 times upper limit of normal 6. Acceptable hematologic status (without hematologic support):
• ANC ≥1000 cells µL
• Platelet count ≥75,000/µL
• Hemoglobin ≥9.0 g/dL 7. All women of childbearing potential must have a negative serum pregnancy test at screening. Male and female subjects must agree to use effective means of contraception (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose. 8. Subjects with a creatinine clearance greater than or equal to 60 mL/min (using the Cockcroft-Gault Equation) for males and females. 1. The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study. 2. Obstructive or symptomatic communicating hydrocephalus 3. Ventriculo-peritoneal or ventriculo-atrial shunts without programable valves or contraindications to placement of Ommaya reservoir 4. Females of childbearing potential who are pregnant, breast feeding, or may possibly be pregnant without a negative serum pregnancy test 5. Serious intercurrent illness, such as progressive systemic (extra leptomeningeal) disease, clinically significant cardiac arrhythmias, uncontrolled systemic infection, symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug, myocardial infarction, stroke, transient ischemic attack within 6 months, seizure disorder with any seizure occurring within 14 days prior to consenting or encephalopathy 6. Active severe non hematologic organ toxicity such as renal, cardiac, hepatic, pulmonary, or gastrointestinal systemic toxicity grade 3 or above. 7. Significant coagulation abnormalities such as inherited bleeding diathesis or acquired coagulopathy with unacceptable risks of bleeding. 8. Patients who had any dose to the spinal cord or whole brain radiation therapy, regardless of when the radiation treatment was delivered. 9. Myelopathy following spinal irradiation greater than 3 weeks prior to the first dose of 186RNL. 10. Systemic chemotherapeutic agents with CNS penetration (such as temozolomide, carmustine, lomustine, capecitabine, carboplatin, vinorelbine, bevacizumab, irinotecan or topotecan) unless they develop or have progressive or persistent leptomeningeal metastases while on these agents. 11. Systemic therapy (including investigational agents and small-molecule kinase inhibitors) within 14 days or 5 half-lives, whichever is shorter, prior first dose of study drug (186RNL). 12. Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug (186RNL). 13. Impaired CSF Flow Study performed on Day -4 to Day -2 based on study imaging and as determined by the investigator.

1. ≥12 years of age and weighing at least 40 kg 2. Progressive meningioma that is amenable to volumetric analysis 3. Has either 1) sporadic meningioma with confirmed NF2 mutation; or, 2) confirmed diagnosis of NF2 disease (revised Manchester criteria); or, 3) at least one NF2-related tumor (with pathogenic germline or proven mosaic NF2 variant) 4. Adequate bone marrow function 5. Has provided written informed consent/assent to participate in the study 1. Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months. 2. Received prior surgery, radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor within 6 months prior to screening. 3. Received an anti- tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), prior to screening. 4. History of an active malignancy within the previous 3 years except for localized cancers that are considered cured, and, in the opinion of the investigator, present a low risk of recurrence. 5. Received another investigational drug within 30 days prior to screening 6. Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dose of IMP.

• Patients must be >= 3 years and < 30 years at the time of study enrollment
• Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation of AFP above institutional normal or > 10 ng/mL or human chorionic gonadotropin (hCG) beta > 100 mIU/mL. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers and cytology must be within 21 days prior to enrollment and within 35 days prior to start of protocol therapy [repeat if necessary]. Serum tumor markers, AFP and hCGbeta must be within 7 days prior to enrollment and start of protocol therapy [repeat if necessary]). Basal ganglia or other primary sites are excluded
• Patients with any of the following pathological elements are eligible: endodermal sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant elements listed above are present. Patients with only mature teratoma are excluded. Patients with pure germinoma admixed with mature teratoma are excluded (would be eligible for pure germinoma protocols)
• Patients must have a cranial magnetic resonance imaging (MRI) with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post operative brain MRI with and without gadolinium. The post operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required (within 14 days prior to study enrollment)
• Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment. Spine MRI with and without gadolinium is recommended (within 14 days prior to study enrollment)
• Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery
• Patients must have CSF tumor markers obtained prior to enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment)
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days prior to enrollment)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age: Maximum serum creatinine (mg/dL)
• 3 to < 6 years: 0.8 (male), 0.8 (female)
• 6 to < 10 years: 1 (male), 1 (female)
• 10 to < 13 years: 1.2 (male), 1.2 (female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: male (1.7), 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment)
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
• Central nervous system function defined as:
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
• Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment
• Protocol therapy must begin within 31 calendar days of definitive surgery or clinical diagnosis. If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery.
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:
• English-, Spanish-, or French- speaking
• Note: Patients who speak a language other than English, Spanish, or French will be allowed to participate in ACNS2021 but will not complete the neurocognitive and quality of life assessments
• No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g., Down syndrome, fragile X, William syndrome, intellectual disability). Patients with NF1 will be allowed to participate
• Additional eligibility criteria for the COG Standardized Neuropsychological Battery only: must be at a site that has a psychologist to administer the battery
• Note: If not eligible for the COG Standardized Battery, patients should still complete the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior Assessment System Third Edition (ABAS-3), and Behavior Assessment System for Children, Third Edition (BASC-3) questionnaires
• Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)
• Patients with only mature teratoma and non-elevated markers upon tumor sampling at diagnosis
• Patients who have received any prior tumor-directed therapy for their diagnosis of NGGCT other than surgical intervention and corticosteroids
• Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or intraoperative evidence of dissemination)
• Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs
• Note: Serum and urine pregnancy tests may be falsely positive due to HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by institutional standards
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

• Patient has confirmed diagnosis of a R/R solid or CNS tumor with a mutation in KIT or PDGFRA (confirmed by local mutational testing of tumor sample) that has progressed despite standard therapy and no alternative treatment option is available OR Confirmed diagnosis of H3K27M mutant glioma that has failed standard therapy or for which no standard therapy that may convey clinical benefit exists, as judged by the Investigator.
• Patients with CNS disease should be on a stable dose (≤10% change) of corticosteroids for at least 7 days prior to first dose of avapritinib, with no plans for dose escalation.
• Disease extent 1. Part 1: All patients must have at least 1 measurable lesion as defined by RECIST v1.1 or RANO (for CNS tumors). If radiation therapy has been administered, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated. 2. Part 2: At least one measurable lesion as defined by RECIST v1.1 (RANO for CNS tumors). If radiation therapy has been administered, at least 1 measurable lesion must not have been irradiated within the previous 12 weeks, or must have clearly progressed since being radiated (per RANO). For up to 5 patients with H3K27M mutant gliomas where there is no standard therapy that may convey clinical benefit as judged by the investigator, progression of disease of a measurable lesion after irradiation is not required.
• A Lansky (≤16 years of age) or Karnofsky (>16 years of age) score of at least 50. If the patient is unable to walk due to paralysis, but is mobile in a wheelchair, the patient is considered ambulatory for the purpose of assessing their performance status.
• Patient agrees to utilize contraception consistent with local regulations
• Patient has any of the following within 14 days before the first dose of study treatment: 1. Platelet count <75 × 109/L (<100 × 109/L if a CNS tumor). 2. Absolute neutrophil count (ANC) <1.0 × 109/L. 3. Hemoglobin <8.0 g/dL (RBC transfusion ≥14 days before test is permitted to meet criterion). 4. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × the upper limit of normal (ULN) for age; except in patients with tumor involvement of the liver who must not have AST and ALT >5 × ULN for age. 5. Total bilirubin >1.5 mg/dL for age; and in presence of Gilbert's syndrome, total bilirubin. > 3 × ULN or direct bilirubin > 1.5 × ULN. 6. Serum creatinine >1.5 × ULN for age. 7. International normalized ratio (INR) or prothrombin time (PT) >ULN (>1.5 × ULN if on prophylactic reversible anticoagulants).
• Patient has a QT interval corrected using Fridericia's formula (QTcF) >470 msec. Patient has a familial or personal history of prolonged QT syndrome or Torsades de pointes.
• Patient has clinically significant, uncontrolled, cardiovascular disease including congestive heart failure Grade III or IV according to the New York Heart Association (NYHA) classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension (>99th percentile for age), or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (eg, Type II second degree heart block or third-degree heart block).
• Patient received the following systemic antineoplastic therapies: 1. Systemic antineoplastic therapy (including experimental therapy within 5 half-lives or 28 days [6 weeks if prior nitrosurea], whichever is shorter). 2. Focal external beam radiotherapy, including stereotactic radiosurgery, within 6 weeks prior to the first dose of avapritinib to either target or non-target lesions. Systemic radiopharmaceuticals, including nonstereotactic radiosurgery, within 2 weeks of the first dose of avapritinib (within 6 weeks for patients with CNS tumors). Craniospinal irradiation within 12 weeks prior to the first dose of avapritinib. 3. All AEs related to other antineoplastic therapies (eg, systemic antineoplastics, radiotherapy) must have resolved to Grade ≤1 (Grade ≤2 for peripheral neuopathy and/or ototoxicity) prior to the first dose of avapritinib.
• Patient has previously received treatment with avapritinib.
• Patient received autologous stem cell transplant (SCT) following myeloablative therapy or chimeric antigen receptor T cell (CAR-T) therapy within 3 months prior to the first dose of avapritinib or prior allogeneic SCT within 1 year and no evidence of Grade 1 or greater graft-versus-host disease and no immunosuppressants for graft-versus-host disease (steroids for primary malignancy being permitted). Patients who received stem cell reinfusion following nonmyeloablative therapy are eligible once they meet the peripheral blood count criteria in Exclusion Criterion #1.
• Patient requires on going treatment or has received treatment within 28 days before the start of avapritinib administration with drugs or foods that are strong CYP3A inhibitors or inducers or EIAEDs (eg, carbamazepine, phenytoin, phenobarbital, and primidone). Please refer to Appendix 1 for a list of these drugs and/or foods.
• Patient has had a major surgical procedure within 14 days of the first dose of study treatment (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures).
• Patient has a history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of avapritinib. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
• Female subjects of childbearing potential who are unwilling, if not post-menopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment. Male subjects who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment. Refer to Section 5.4.2 for acceptable methods of contraception.
• Patient is pregnant
• Patient is breastfeeding.
• Patient has prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results.
• History of thrombosis requiring treatment within the past 6 months.
• Patients who require anticoagulants, with the exception of stable doses of prophylactic reversible anticoagulants.
• Patients who are unable to swallow tablets (in Part 1) or mini-tablets (in Part 2) within the sprinkle capsules.
• Patients with a known risk of intracranial bleeding, such as a brain aneurysm that has not been removed or repaired, or a history of intracranial bleeding within the past year, or radiographic evidence of hemorrhage on Screening MRI. Exceptions are patients with primary CNS tumors who are eligible unless CNS bleeding has occurred within 2 weeks of the first dose of avapritinib and patients with punctate hemorrhages <3 mm.
• History of a seizure disorder that is not well controlled on current antiepileptic medications. EIAEDs carbamazepine, phenytoin, phenobarbital, and primidone are prohibited.
• Patient is unwilling or unable to comply with scheduled visits, treatment administration plan, laboratory tests, or other study procedures and study restrictions

• Histologically proven primary CNS diffuse large b-cell lymphoma confirmed by one of the following:
• Brain biopsy or resection
• Cerebrospinal fluid
• Vitreous fluid
• At least one measurable, contrast-enhancing lesion in the brain (>= 1 cm in length), CSF or vitreous (intraocular lymphoma)
• No prior organ transplantation to exclude post-transplant lymphoproliferative disorders
• No prior chemotherapy or radiation therapy for lymphoma
• No prior allogeneic stem cell transplantation
• Use of systemic corticosteroids (dexamethasone up to 24 mg/day or equivalent) for disease control or improvement of performance status to be tapered as fast as clinically safe after initiation of therapy is permissible
• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown and an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, female of childbearing potential (FCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) =< 7 days prior to registration
• Karnofsky performance scale (KPS) >= 40 (>= 50 for patients older than 60 unless related to lymphoma on investigator's opinion)
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Calculated creatinine clearance >= 50 mL/min by Cockcroft-Gault formula
• Total Bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
• No evidence of non-Hodgkin's lymphoma (NHL) outside CNS
• No prior history of NHL
• No history of autoimmune disorder. Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as Systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
• Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (except short course of systemic corticosteroids for disease control or improvement of performance status or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if < 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
• Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study
• No prior or concurrent malignancies with exception of surgically cured carcinoma in situ (CIS) of the uterus, carcinoma of the skin without evidence of disease for >= 5 years
• No concurrent malignancy requiring active therapy
• No untreated hepatitis C virus (HCV) infection with detectable HCV viral load
• No untreated chronic hepatitis B virus (HBV) infection with detectable HBV viral load
• No untreated human immunodeficiency virus (HIV) infection or with detectable viral load or with CD4+T-cell count of less than 500/mm^3
• No history of HIV infection and evidence of Epstein Barr virus (EBV)-related primary central nervous system lymphoma (PCNSL)
• Inability to tolerate anticoagulation with acetylsalicylic acid, warfarin, or direct oral anticoagulants
• No other investigational agent
• No history of severe hypersensitivity reaction to any monoclonal antibody
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to or other agents used in study
• Sulfonamide drugs, trimethoprim, salicylates, nonsteroidal anti-inflammatory drugs, penicillin, vitamin C, ciprofloxacin, and proton pump inhibitors should be held at least 48 hours prior to methotrexate administration

• Stratum I
• Patients must be less than 18 years of age at the time of diagnosis.
• Patients must have histological verification of the diagnosis of Langerhans cell histiocytosis according to the criteria described in Section 6.1
• Signed informed consent form
• Stratum II
• Patients of Stratum I who have:
• Progressive disease (AD worse) in non-risk organs after 6 weeks (Initial Course
• AD intermediate or worse in non-risk organs or AD better in risk organs after 12 weeks (Initial Course 2)
• Disease progression (AD worse) in non-risk organs at any time during continuation treatment
• Active disease at the end of Stratum I treatment
• Disease reactivation in non-risk organs at any time after completion of Stratum I treatment
• Stratum III
• Patients from Stratum I who fulfill the following criteria:
• AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD intermediate in risk organs after week 12 (after Initial Course 2).
• Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as
• Hb <70 g/L (<7.0 g/dl) and/or transfusion dependency
• PLT <20 x109/L (20,000/μL) and/or transfusion dependency (both criteria have to be fulfilled) AND/OR
• Liver dysfunction (or digestive involvement with protein loss)
• Total protein <55 g/L or substitution dependency
• Albumin <25 g/L or substitution dependency (at least one of the two criteria to be fulfilled)
• Stratum IV
• Patients from Stratum I or Stratum III who fulfill the following criteria:
• AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD intermediate in risk organs after week 12 (after Initial Course 2) of Stratum I OR
• AD worse after the 2nd and 3rd 2-CdA/Ara-C course, and those AD worse or AD intermediate after the 4th 2-CdA/Ara-C course of Stratum III AND
• Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as defined in Table XI (see Section 10.3.1).
• Informed consent: All patients or their legal guardians (if the patient is <18 years of age) must sign an Ethics or institutional Review Board approved consent form indicating their awareness of the investigational nature and the risks of this study. When appropriate, younger patients will be included in all discussions in order to obtain assent.
• Adequate organ function: Patients should have adequate hepatic, renal, cardiac and pulmonary function to undergo reduced intensity HCT based upon local institutional guidelines, or at a minimum meet requirements noted in eligibility checklist Appendix A-VIII_1. However, significant hepatic and pulmonary dysfunction, if secondary to underlying LCH disease activity, will not exclude patients from protocol enrollment and should be discussed with the National PI Coordinator and the Coordinating Principal Investigator.
• Stratum V
• All patients with verified diagnosis of LCH and MRI findings consistent with ND-CNSLCH irrespective of previous treatments (also those not registered to other Strata ofLCH-IV).
• Patients with isolated tumorous CNS-LCH (including isolated DI with mass lesion in the hypothalamus-pituitary axis). In patients with already established diagnosis of LCH and radiologic finding of CNS lesions compatible with LCH, a biopsy of the lesion is not obligatory. In all other cases a biopsy of the lesion is needed for inclusion into the study
• Stratum VI -- Patients with newly diagnosed SS-LCH and localization other than "multifocal bone",isolated tumorous CNS lesion, or isolated "CNS-risk" lesion.
• Stratum VII -- All patients registered in LCH IV (regardless of treatment) as long as consent for longterm follow-up has not been withheld.
• Stratum I
• Pregnancy (patients of child-bearing age must be appropriately tested before chemotherapy)
• LCH-related permanent consequences (e.g. vertebra plana, sclerosing cholangitis, lung fibrosis, etc.) in the absence of active disease
• Prior systemic therapy
• Stratum II
• Patients with progressive disease in risk organs
• Permanent consequences (e.g. sclerosing cholangitis, lung fibrosis, etc.) without evidence of active LCH in the same organ or in any other locations
• No written consent of the patient or his/her parents or legal guardian
• Stratum III
• The presence of any of the following criteria will exclude the patient from the study:
• Isolated sclerosing cholangitis without evidence of active hepatic LCH as the only evidence of risk organ involvement.
• Inadequate renal function as defined by serum creatinine > 3x normal for age
• Stratum IV
• Pulmonary failure (requiring mechanical ventilation) not due to active LCH.
• Isolated liver sclerosis or pulmonary fibrosis, without active LCH.
• Uncontrolled active life-threatening infection.
• Decreased renal function with a GFR of less than 50ml/1.73m2/min.
• Pregnancy or active breast feeding
• Failure to provide signed informed consent
• Stratum VI
• Patients with SS-LCH who have an isolated tumorous CNS lesion (they are eligible for Stratum V),
• Patients with isolated "CNS-risk" or multifocal bone lesions (they are eligible for Stratum I, Group 2)

• Patients must be >= 2 years and =< 21 years at the time of enrollment
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG) without a BRAFV600E mutation as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 (NCT02402244) and that has not been treated with any modality besides surgery. Note: Patients may be newly-diagnosed OR previously diagnosed, and there is no required time frame between biopsy/surgery and treatment initiation.
• Patients with residual tumor after resection or progressive tumor after initial diagnosis (with or without surgery) who have not received treatment (chemotherapy and/or radiation) are eligible
• Patients must have two-dimensional measurable tumor >= 1 cm^2 to be eligible
• Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization [WHO] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
• Patients with metastatic disease or multiple independent primary LGG are eligible
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows (performed within 7 days prior to enrollment):
• Age: Maximum Serum Creatinine (mg/dL)
• 2 to < 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female)
• 6 to < 10 years: 1 mg/dL (male); 1 mg/dL (female)
• 10 to < 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female)
• 13 to < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
• >= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect [unconjugated] bilirubin levels as long as their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
• Albumin >= 2 g/dL (performed within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram (performed within 4 weeks prior to enrollment)
• Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) (performed within 4 weeks prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (performed within 7 days prior to enrollment)
• Platelets >= 100,000/uL (unsupported) (performed within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (performed within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for age, height, and gender at the time of enrollment (with or without the use of anti-hypertensive medications)
• Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications)
• Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks prior to enrollment
• For all patients, a magnetic resonance imaging (MRI) of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site(s) of primary disease) with and without contrast must be performed within 4 weeks prior to enrollment
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Patients must have the ability to swallow whole capsules
• All patients have signed an appropriate consent form and Health Insurance Portability and Accountability Act (HIPAA) authorization form (if applicable)
• All patients and/or their parents or legal guardians must sign a written informed consent
• All patients have been consented and enrolled on APEC14B1 (NCT02402244) followed by enrollment on the ACNS1833 Pre-Enrollment Eligibility Screening (Step 0) on the same day to complete the Rapid Central Review
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention is permitted
• Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
• Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
• Patients may not be receiving any other investigational agents
• Patients with any serious medical or psychiatric illness/condition, including substance use disorders or ophthalmological conditions, likely in the judgment of the investigator to interfere or limit compliance with study requirements/treatment
• Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible
• Female patients who are pregnant are not eligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants are not eligible
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 12 weeks after stopping study therapy are not eligible.
• Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
• Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented
• Symptomatic heart failure
• New York Health Association (NYHA) class II-IV prior or current cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular pressure (IOP) > 22 mmHg or ULN adjusted by age are not eligible
• Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of surgical biopsy, placement of a vascular access device or cerebral spinal fluid (CSF) diverting procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt.
• Note: Patients must have healed from any prior surgery
• Patients who have an uncontrolled infection are not eligible

1. 1 month of age up to < 18 years of age at the time of signing the informed consent. 2. Received HSCT within the past 6 months. 3. Diagnosis of TMA that persists despite initial management of any triggering condition. 4. Body weight ≥ 5 kilograms. 5. Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception starting at Screening and continuing until at least 8 months after the last dose of ravulizumab. 6. Participants must be vaccinated against meningococcal infections if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. Participants must be re-vaccinated against Haemophilus influenzae type b and Streptococcus pneumoniae if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. All participants should be administered coverage with prophylactic antibiotics according to institutional post-transplant infection prophylaxis guidances, including coverage against Neisseria meningitidis for at least 2 weeks after meningococcal vaccination. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis coverage against Neisseria meningitidis the entire Treatment Period and for 8 months following the final dose of ravulizumab. 1. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' deficiency (activity < 5%). 2. Known Shiga toxin-related hemolytic uremic syndrome. 3. Positive direct Coombs test. 4. Diagnosis or suspicion of disseminated intravascular coagulation. 5. Known bone marrow/graft failure. 6. Diagnosis of veno-occlusive disease. 7. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer). 8. Unresolved meningococcal disease. 9. Presence or suspicion of sepsis (treated or untreated) within 7 days prior to Screening. 10. Pregnancy or breastfeeding. 11. Hypersensitivity to murine proteins or to 1 of the excipients of ravulizumab. 12. Previously or currently treated with a complement inhibitor.

• Advanced or metastatic solid or primary CNS tumor which has failed standard of care therapies
• Evidence of an activating RET gene alteration in the tumor and/or blood
• Measurable or non-measurable disease
• Karnofsky (participants 16 years and older) or Lansky (participants younger than 16) performance score of at least 50
• Participant with primary CNS tumors or cerebral metastases must be neurologically stable for 7 days prior and must not have required increasing doses of steroids within the last 7 days
• Adequate hematologic, hepatic and renal function.
• Ability to receive study drug therapy orally or via gastric access
• Willingness of men and women of reproductive potential to observe conventional and effective birth control
• Major surgery within two weeks prior to planned start of LOXO-292
• Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292
• Active uncontrolled systemic bacterial, viral, fungal or parasitic infection
• Clinically significant active malabsorption syndrome
• Pregnancy or lactation
• Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the participant required a modification to current thyroid medication in the 7 days before start of LOXO-292)
• Uncontrolled symptomatic hypercalcemia or hypocalcemia
• Known hypersensitivity to any of the components of the investigational agent, LOXO-292 or Ora-Sweet® SF and OraPlus®, for participants who will receive LOXO-292 suspension
• Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s])

• Histologically or cytologically documented locally advanced or metastatic solid tumor malignancy.
• Progressed or was intolerant to all available therapies known to confer clinical benefit appropriate for their tumor type, and for which the patient was eligible and willing to receive, or refused SOC treatments that are perceived to have marginal clinical benefit.
• Adequate bone marrow, kidney and liver function.
• Performance status of 0 or 1.
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 except for AEs not constituting a safety risk by Investigator judgement.
• Prior treatment targeting ILT2 and/or ILT4 or targeting HLA-G.

Inclusion: 1. Histologically confirmed relapsed or refractory solid tumor as follows:
• For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
• For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
• For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement. Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners is required OR availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or have refractory disease and at least evaluable disease in at least one site other than bone marrow that can be followed by imaging. 2. Age ≥2 and <21 years at the time of study entry. 3. Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age. 4. Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed). 5. Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits. 6. Adequate liver function, including:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
• Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome. 7. Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or INRC for neuroblastoma. Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component). 8. Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia. 9. Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit. Exclusion: 1. Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 portion: prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ and did not progress while on these medications are eligible. 2. Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination. 3. Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.) 4. Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas. 5. Prior irradiation to >50% of the bone marrow (see Appendix 9). 6. Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry. 7. Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries. 8. For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX. 9. Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for >14 days. 10. Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable. 11. Hereditary bone marrow failure disorder. 12. QTc >470 msec. 13. History of clinically significant or uncontrolled cardiac disease, including:
• History of or active congestive heart failure; if patient had congestive heart failure resolve and >1 year from resolution, patient will be considered eligible;
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
• Diagnosed or suspected congenital or acquired prolonged QT syndrome;
• Need for medications known to prolong the QT interval;
• Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
• Left ventricular ejection fraction <50% or shortening fraction <28%. 14. Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy). 15. Severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study. 16. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.

• Patients with histologically confirmed solid tumor malignancies with residual tumors present that require standard of care chemotherapy for a minimum number of cycles. All anatomical sites and all tumor histologies are eligible including central nervous system tumors. Both newly diagnosed and/or newly relapsed patients are eligible.
• Patients ages 8
•25 years
• In the opinion of the investigator, patients must be thought to be able to lie still for imaging without sedation for 20
•30 minutes.
• Patients must have a performance status of > 50% (Lansky or Karnofsky).
• Patients of childbearing potential must have a negative urine or serum pregnancy test as per institution's standard of care within 7 days prior to [18F]FLT PET/CT imaging.
• Ability to understand and the willingness to sign a written informed consent/assent.
• Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals of similar chemical or biologic composition to [18F]FLT
• Newly diagnosed subjects who had prior chemotherapy or radiotherapy before enrollment in the study. Relapsed patients are eligible prior to starting their relapsed chemotherapy regimen if they meet the other eligibility criteria.
• Subjects for whom chemotherapy is not a standard of care primary therapy option.
• Patients who are pregnant or breast-feeding.
• Patients with no residual tumor (i.e. complete resection at diagnosis or relapse).