• Age \>= 1 year(s) old (no maximum age)

• Radiologic appearance of diffuse midline glioma of the pons, including diffuse infiltration of \>= 50% of the pons on MRI, with or without extension to the midbrain and/or medulla oblongata with at least 1 of the 3 brainstem symptoms (cranial nerve deficit, long tract sign, or cerebellar sign)

‣ If all features of this clinicoradiologic criteria are met, then patients can continue on protocol with or without a biopsy

⁃ If all features of this clinicoradiologic criteria are not met, patients must receive a brainstem lesion biopsy to be treated on protocol. If this cannot be completed, patients will be withdrawn from the study

⁃ If biopsy has already been completed at an outside institution, the outside pathology report will be reviewed ahead of trial enrollment. The pathology specimen will then be sent to Mayo Clinic for further review, but will not delay study enrollment

• Able to undergo MRI Brain

• Negative urine pregnancy test completed =\< 7 days prior to registration, for women of childbearing potential only

• Primary language of English or Spanish for patients and their caregiver

• Patient or caregiver willing and able to provide written informed consent

• Caregiver able to complete questionnaires by themselves or with assistance

• Willing to return to enrolling institution for follow-up during the active monitoring phase of the study