Research participants with other clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results history Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patients ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results Patients with any clinically significant unrelated systemic illness that would compromise the patients ability to tolerate protocol therapy Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that will likely interfere with the study procedures or results Concurrent Illness\r\n* Patients with active autoimmune disease or documented history of autoimmune disease/syndrome that requires ongoing systemic steroids or systemic immunosuppressive agents, except \r\n** Patients with vitiligo or resolved asthma/atopy\r\n** Patients with hypothyroidism stable on hormone replacement or Sjogrens syndrome \r\n* History of or ongoing pneumonitis or significant interstitial lung disease\r\nNote: This would include non-infectious pneumonitis that required steroid use\r\n* Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patients ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results\r\n* Patients with other current malignancies\r\n* Patients with known hypermutated brain tumors including those with CMMRD and Lynch syndrome are ineligible for enrollment in Strata A, B, D and E\r\n* Patients who have received a solid organ transplant EXCLUSION CRITERIA FOR STRATUM C: Concurrent illness\r\n* Patients with active autoimmune disease or documented history of autoimmune disease/syndrome that requires ongoing systemic steroids or systemic immunosuppressive agents, except \r\n** Patients with vitiligo or resolved asthma/atopy\r\n** Patients with hypothyroidism stable on hormone replacement or Sjogrens syndrome \r\n* History of or ongoing pneumonitis or significant interstitial lung disease\r\n* Note: This would include non-infectious pneumonitis that required steroid use\r\n* Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patients ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results\r\n** Exception to this is the presence of gastrointestinal polyps/adenomas and non-metastatic carcinomas, and history of any previous malignancies in patients with CMMRD which will be allowed in this study\r\n* Patients who have received a solid organ transplant Patients with any clinical significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that is likely to interfere with the study procedures or results Clinically significant patient history which in the judgment of the principal investigator would compromise the patients ability to tolerate high-dose Clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), which in the judgment of the principal or associate investigator would compromise the patients ability to tolerate this therapy or are likely to interfere with the study procedures or results STRATUM A: Participants with other clinically significant medical disorders (serious infections or significant cardiac, pulmonary, hepatic, psychiatric, gastrointestinal [GI] disease, or other organ dysfunction) that in the investigators judgment could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or results STRATUM B: Participants with other clinically significant medical disorders (serious infections or significant cardiac, pulmonary, hepatic, psychiatric, GI disease, or other organ dysfunction) that in the investigators judgment could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or results STRATUM C: Participants with other clinically significant medical disorders (serious infections or significant cardiac, pulmonary, hepatic, psychiatric, GI disease, or other organ dysfunction) that in the investigators judgment could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or results Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), likely interfere with the study procedures or results Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction Clinically significant unrelated systemic illness (including but not limited to active life threatening infection, cardiac or neurologic events, current hospital admission for a coexisting comorbid illness), which would make it impossible for the patient to tolerate re-irradiation or systemic chemotherapy or likely to interfere with the results Clinically significant medical disorders that could compromise the ability to tolerate protocol therapy or that would interfere with the study procedures or results history Patients with clinically significant unrelated systemic illness (including autoimmune disease, serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the principal or associate investigators would compromise the patients ability to tolerate this therapy or are likely to interfere with the study procedures or results Clinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the principal investigator (PI) would compromise the patients ability to tolerate protocol therapy or significantly increase the risk of complications Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patients ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results Concurrent Illness\r\n* Patients with any clinically significant unrelated systemic illness (serious infections grade >= or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patients ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results\r\n* Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patients first malignancy has been in remission for at least years from the end of treatment Clinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the principal investigator (PI) would compromise the patients ability to tolerate protocol therapy or significantly increase the risk of complications Clinically significant systemic illness (e.g., serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the principal investigator (PI) would compromise the patients ability to tolerate protocol therapy or significantly increase the risk of complications; peripheral nerve symptoms from prior therapies or from tumor compression > grade Clinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the PI would likely compromise the patients ability to tolerate protocol therapy or significantly increase the risk of complications Clinically significant unrelated illness which would, in the judgment of the treating physician, compromise the patient's ability to tolerate the investigational agent or be likely to interfere with the study procedures or results. Concurrent Illness Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results. Patients with any clinically significant systemic illness, including serious infection, pulmonary, hepatic, or other organ impairment, that would compromise tolerance and/or timely completion of protocol therapy Patients with any clinically significant unrelated systemic illness (e.g., serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patients ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results Research participants with other clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results Known severe, active co-morbidity, defined as follows:\r\n* Any clinically significant unrelated systemic illness, medical condition, or other factor, which at the discretion of the Principal Investigators, would interfere in the safe and timely completion of study procedures, compromise the patients ability to tolerate the protocol therapy, or is likely to interfere with the study procedures or results Clinically significant systemic illness with manifestations of significant organ dysfunction which in the judgment principal investigator (PI) or associated investigator (AI) would render the patient unlikely to tolerate the protocol therapy or complete the study Clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the Principal or Associate Investigator would compromise the patients ability to tolerate PEG-Intron or are likely to interfere with the study procedures or results Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patients ability to tolerate protocol therapy or would likely interfere with the study procedures or results Clinically significant systemic illness (e.g. serious active infections or significant vital other organ dysfunction), that in the judgment of the principal investigator (PI) would likely compromise the patients ability to tolerate protocol therapy or significantly increase the risk of complications RECURRENT/ PROGRESSIVE DIPG (STRATUM ): Patients have any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the ability of the patient to tolerate protocol therapy or put them at additional risk for toxicity or would interfere with the study procedures or results NON-PROGRESSED DIPG (STRATUM ): Patients have any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the ability of the patient to tolerate protocol therapy or put them at additional risk for toxicity or would interfere with the study procedures or results Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patients ability to tolerate protocol therapy or would likely interfere with the study procedures or results Clinically significant untreated system illness, such as seriously infections, autoimmunity or organ dysfunction, which in the judgement of the Principal or Associate Investigators would compromise the patients ability to tolerate the investigational agents or are likely to interfere with the study procedures or results Clinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgement of the Principal or Associate Investigators would compromise the patients ability to tolerate the investigational agents or are likely to interfere with the study procedures or results Clinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgment of the Principal or Associate Investigators would compromise the patients ability to tolerate the investigational agents or are likely to interfere with the study procedures or results