Apart from that reason of lack of infrastructure, another key point is direct access to Tibet from those areas. As China is very strict on any activities again Tibet, like free Tibet and do not Nepal to let them other used Nepali Land for demonstration against Tibet and China, which is another strong reason why these area are restricted for trekking. Talking about Kanchenjunga there are several passes on Olangchungola toward Tibet and northern base camp area are still very basic in term of accommodation and foods so this area is still under tag of restricted region to trek.
Makalu Base Camp area is itself not restricted but if one is trekking toward Barun Valley and head to Kimathangka then it is another important border on Tibetan side, although area is bit developed with lower terrain and large villages.
Manaslu Trekking Permit
Upper Mustang, The Last forbidden kingdom or sometimes also known as The Little Tibet is one of the most powerful restricted area because it is more easily connected to Tibet as it used to serve as Trans Himalayan Salt Trade Route with Tibet, cause people from Mustang, Manang they used to trail to connect with Tibet before for trading salts or whatever other basic stuffs. Apart from that upper mustang has excellent history as well as culture so it most be preserved for future which is main reason why there is strict controlled tourism in Upper Mustang with limited number of visitor per year.
Upper Dolpa, which is almost inaccessible for foreigner and local Nepali People, cause most of village in Dolpo and beyond high passes and surrounded by Himalayas on entire side. It comes in limelight from the time when famous movie named Caravan win Oscar award, which is mainly basis of caravan of yak heading toward Tibet for trading. Still people from Upper Dolpa directly depends upon Tibet for entire stuffs as they go toward Tibetan Side frequently on a large group and bring necessary stuffs laden over yak. Because the area is on remote part untouched by motor road, only way to get connected with major cities of Nepal is Jhupal Airport, where flight rates are expensive as well as uncertain because of bad weather.
If you want to know more about, details of those restricted area along with details itinerary then refer to following links