STEP I: Patients must not have active, uncontrolled seizure disorder; patients must have had no seizures in the last 6 months Patients with uncontrolled seizure disorder are not eligible; (patients with seizure disorders that do not require antiepileptic drugs, or are well controlled with stable doses of antiepileptic drugs remain eligible) Patients with active seizures or a history of uncontrolled seizure disorder, including focal or generalized seizure within the past year Patients with a history of seizure disorder requiring antiepileptic medication or brain metastases with seizures are NOT eligible for participation History of seizures, prior traumatic brain injury, prior stroke, or other predisposing risk of seizure (excluding CNS metastasis) History of seizure disorder requiring antiepileptic medication or brain metastases with seizures Seizures disorder not controlled by anti-seizure medications Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child Any history of epilepsy or a seizure disorder or any known prior seizures. Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child Adequate central nervous system function defined as:\r\n* Subjects with seizure disorder may be enrolled if on anticonvulsants and seizures are well controlled Patients with a history of active seizures (or a single confirmed seizure event) in the last 2 years from the time of registration Uncontrolled seizure disorder (ie, seizures within the past 2 months). Uncontrolled seizure disorder (ie, seizures within the past 2 months). For subjects with ATRT only, subject must have seizures that are stable, not increasing in frequency or severity and controlled on current anti-seizure medication(s) for a minimum of 21 days prior to the planned first dose of tazemetostat Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child Patients with a seizure disorder are study eligible if seizures are controlled on anticonvulsants Patients with a history of uncontrolled seizures or who are not on anti seizure medication (e.g., Phenytoin 100 mg PO t.i.d. or Keppra 500 mg po bid) before the procedure Patients with seizure disorder may be enrolled if seizures are well-controlled (i.e., patients must not have required rescue medications for uncontrolled seizures within 14 days prior to enrollment) Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs will be excluded Patients with a history of seizure disorder (except infant febrile seizures) Patients with seizure disorder may be enrolled if on anticonvulsants and if seizures are well controlled Patients with a high risk of seizures should be excluded from the protocol (e.g. those patients with an uncontrolled seizure disorder, and/or patients who have had a focal or generalized seizure within the last 12 months) Patients with a history of encephalitis, multiple sclerosis, or seizures within the last year (from seizure disorder or brain metastasis) should be excluded from this clinical trial History of seizure disorder requiring antiepileptic medication or brain metastases with seizures Patients must not have active, uncontrolled seizure disorder; patients must have had no seizures in the last 6 months Comorbid conditions: patients are unable to participate due to the following:\r\n* Generalized or partial seizure disorder that is uncontrolled at the time of registration; the definition of controlled generalized seizures is patients must be on a stable dose of anti-seizure medication and without generalized seizures for at least 10 days prior to registration; the definition of controlled partial seizures is patients must be on a stable dose of anti-seizure medication for at least 10 days prior to registration; patients with occasional breakthrough partial seizures are allowed at treating physician’s discretion\r\n* Grade 3 or 4 thromboembolic disease within 6 months (mo) of registration\r\n* Known history of prolonged QT syndrome Patients with epilepsy, seizures, or predisposing factors for seizure as judged by the investigator. History of seizure any time in the past for any reason or any condition that may predispose to seizures. Patients with seizure disorder may be enrolled if seizures are well controlled Any history of seizures or medical condition which lowers seizure threshold Patients with a prior seizure disorder requiring anti-convulsant therapy are not eligible to receive nelarabine. For the purposes of this study, this includes any patient that has received anticonvulsant therapy to prevent/treat seizures in the prior two years. Subjects with seizure disorder may be enrolled if on anticonvulsants and seizures are well controlled History of seizures (unless seizure free for 5 years); Patients with active seizures or a history of seizure are not eligible for study entry, with the exception of patients with documented febrile seizure Intractable seizures while on adequate anticonvulsant therapy—more than 1 seizure per week for the past 2 months Intractable seizures while on adequate anticonvulsant therapy—more than 1 seizure per month for the past 2 months